性别与人类基因组

性别问题与人类基因组有许多方面的关系：对核基因组的重视程度远大于线粒体基因组、基础科学研究的水平、临床决策和更广泛的社会影响。其中临床决策关系到两个方面：一方面是生殖决策,另一方面是诊断性和预测性检验;女权主义者为说明这些问题提供了一个有用的生命伦理学基础。     

No association of PTGDR -441C/T polymorphism with asthma in a North Indian population

Background: Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in the PTGDR gene have been suggested to be involved in the mechanism of asthma. Objective: This is the first study conducted in India, investigating the role of PTGDR −441C/T promoter polymorphism in asthma pathogenesis. Methods: A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The PTGDR−441C/T polymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR). Results: Statistical analysis of the results between asthma cases and controls for the PTGDR −441C/T polymorphism showed Chi² (χ²) = 0.29, OR = 0.95, 95% CI (0.70–1.15) and p = 0.599. Neither the genotypic nor the allelic frequencies observed for the PTGDR −441C/T polymorphism, were significantly associated with asthma or asthma phenotypes. Conclusions: The PTGDR −441C/T polymorphism is not associated with asthma or its phenotypes in the studied North Indian population.     

GnRH-a联合低剂量HCG诱发卵母细胞成熟在行PGD/PGS助孕患者中的应用

目的:探讨促性腺激素释放激素拮抗剂(GnRH-ant)方案中促性腺激素释放激素激动剂(GnRH-a)联合低剂量绒促性素(HCG)扳机对行胚胎植入前遗传学诊断/筛查(PGD/PGS)助孕患者促排卵的效果。方法:回顾性分析2015年1月至2016年3月在我院因女方染色体异常行GnRH-ant方案中GnRH-a联合低剂量HCG双扳机诱导卵泡成熟的PGD/PGS助孕患者79例(A组),根据年龄、抗苗勒管激素(AMH)、基础卵泡刺激素(FSH)匹配选取行拮抗剂方案促排卵并单纯使用HCG扳机诱导卵泡成熟患者79例(B组)作对照,比较两组促排卵特点及促排卵结局。结果:两组促性腺激素总量、促排天数、HCG日雌二醇(E2)、HCG日孕酮(P)、HCG日黄体生成素(LH)、回收卵数、2个原核(2PN)数、第3天(D3)胚胎数、活检正常胚胎数、新发异常率差异均无统计学意义(P0.05)。与B组相比,A组获成熟卵数、D3优质胚胎数、形成囊胚数、优质囊胚数及优质囊胚率明显升高(P0.05),检测后正常的胚胎数虽然两组差异无统计学意义,但A组有升高趋势,两组OHSS发生率无明显差异(P0.05)。结论:GnRH-ant方案中GnRH-a联合HCG诱发卵母细胞成熟改善了行PGD/PGS助孕患者促排结局。     

植入前遗传学诊断/筛查技术指征进展

植入前遗传学诊断/筛查(PGD/PGS)技术发展多年,其指征始终存在争议。PGD指征较为明确,单基因遗传病、染色体异常人群、人类白细胞抗原(HLA)配型为其适用人群。PGS的指征争议较多,主要面向反复流产、反复植入失败、高龄人群,目的是提高妊娠率及活产率。然而第一代PGS技术[PGS#1,卵裂球活检及荧光原位杂交(FISH)-PGS]技术未显示明显效果,甚至降低了妊娠率及活产率。第二代PGS技术(PGS2.0)增加了严重男性因素不育为指征,其核心为囊胚活检及全染色体筛查(CCS),对上述人群的临床效果较为明显,降低了流产风险并提高了成功率及活产率。PGS2.0已极大地改变了辅助生殖技术(ART)面貌,可能成为未来生殖中心对所有患者的一个常规项目。目前仍然需要多中心前瞻性随机病例对照研究重新评估PGS。     

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

Preimplantation genetic diagnosis (PGD) using fluorescence in situ hybridisation probes was carried out for 59 couples carrying reciprocal translocations. Before treatment, 85% of pregnancies had resulted in spontaneous miscarriage and five couples had achieved a healthy live-birth delivery. Following treatment, 33% of pregnancies failed and 21of 59 couples had a healthy live-born child. The accuracy of diagnosis was 92% (8% false abnormal and 0% false normal results). The overall incidence of 2:2 alternate segregation products was 44% however, products consistent with 2:2 adjacent segregation were ∼twice as likely from male heterozygotes, and those with 3:1 disjunction were three times more likely from female heterozygotes. Our results indicate that up to three stimulation cycles per couple would give an ∼50% chance of a successful live birth, with the risk of miscarriage reduced to the level found in the general population. In our study, 87% of all normal/balanced embryos available were identified as being suitable for transfer. We conclude that PGD provides benefit for couples with high-risk translocations by reducing the risk of miscarriage and avoiding a pregnancy with an unbalanced form of the translocation; however, for fertile carriers of translocations with a low risk of conceiving a chromosomally unbalanced offspring, natural conception may be a more viable option.     

G6PD／6PGD定量比值法检测新生儿女性杂合子的临床分析

目的探讨G6PD／6PGD定量比值法检测女性杂合子的临床意义。方法使用G6PD／6PGD定量比值法对广西医科大学第四附属医院2005年1月至2008年1月出生的4124名新生儿的脐血进行G6PD缺乏症检测。结果女性杂合子检出率占估计值18．09％。结论G6PD／6PGD定量比值法在检测女性杂合子中的实际检出率低，容易造成大部分杂合子女性漏诊，对一级亲属中有G6PD缺乏者的高危女性应提高其防范意识，减少G6PD缺乏症对新生儿的危害。     

昆明地区孕妇夫妇G6PD缺乏症的筛查研究

本文采用G6PD/ 6PGD比值法 ,对 1998年 9月～ 2 0 0 1年 8月来我院门诊就诊的 16 97对孕妇夫妇 (共 3394例 )进行G6PD缺乏症筛查。结果表明 :男性G6PD缺乏症发生率为 3 48% ,女性发生率为 5 30 % ,从而得出昆明地区G6PD缺乏症的基因频率为 0 0 34 8。昆明作为此症的高发地区 ,广泛开展孕妇夫妇G6PD缺乏症筛查工作可使临床医生对缺乏症患者进行必要的处理 ,并帮助她们提高防患意识 ,以避免受到氧化物质的损害 ,从而提高优生优育水平。同时 ,本研究表明 ,G6PD/ 6PGD比值法能较为有效地检出女性杂合子 ,建议广泛应用于临床检测。     

Strategies and outcomes of PGD of familial adenomatous polyposis

Owing to adult onset of hereditary cancer, prenatal diagnosis (PND) raises numerous ethical issues on the acceptability to terminate an affected pregnancy (TOP). PND for these disorders is often considered as unacceptable by couples as well as geneticists and legal or ethical authorities, but preimplantation genetic diagnosis (PGD), even if subject to controversy, seems to be a more acceptable option. Therefore, many couples, who do not want to transmit their cancer to their children, consider PGD as their only reproductive option. This article describes our experience of PGD for familial adenomatous polyposis (FAP). Twelve couples were referred between 2000 and 2005. We developed PGD tests to detect the mutation alone, but we rapidly set up multiplex PCR combining mutation detection and indirect diagnosis. Finally, we set up duplex and triplex indirect diagnoses to be able to offer a PGD, whatever mutation was involved in familial cases. PGD strategies were based on (i) a new double allele-specific PCR approach (D-ARMS) allowing the detection of the wild-type and mutated allele; (ii) PCR fragments sizing and (iii) restriction length polymorphisms. For the 12 referrals, we developed eight tests, and 11 cycles have been performed for four couples, resulting in eight embryo transfers and five pregnancies, with the birth of one healthy boy and two ongoing pregnancies. We are now able to propose PGD to most couples at risk of transmitting FAP to their offspring, whether the mutation is familial or occurred de novo.     

染色体病在胚胎植入前遗传学诊断中的研究与发展

随着辅助生殖技术的发展,越来越多的不孕患者通过这项高科技技术得到了自己的后代,但临床发现一部分患者在进行数次辅助生殖助孕后,仍然无法受孕;有的患者即使具有良好的内膜容受性及形态优质的胚胎仍然会发生反复流产.上世纪80年代末,植入前遗传学诊断的出现,使人们认识到这些问题很可能与胚胎染色体异常有关,并运用于临床,大大提高了IVF的植入率及临床妊娠率,使具有遗传缺陷的夫妇能生育健康的后代.因此,本文从分子细胞遗传学角度综述导致植入前胚胎染色体异常的机理与影响因素,荧光原位杂交技术在植入前胚胎染色体异常检测中发挥的作用,以及植入前遗传学诊断在染色体异常方面的研究进展,及其对辅助生殖技术的影响.     

基因测序技术在生殖领域的应用进展

基因测序技术自被发明以来在生命科学领域的研究中发挥着重要作用,利用测序技术对辅助生殖技术(ART)后代进行基因水平检测来评估ART的安全性,是一种非常有效的手段。而利用测序技术对植入前胚胎进行基因检测,不仅可以进行非整倍体筛查来选择优质胚胎进行移植,提高胚胎种植率,还可以避免遗传性疾病在家系内的传递;另外,利用测序技术对不孕不育患者进行基因方面检测,从而发现一些高敏感的致病基因,对于了解不孕不育疾病机理、发现治疗方案提供新的思路。